Robert wake time-resolved breast imaging device

ABSTRACT

A photodetection circuit for use in a laser imaging apparatus comprises a photodetector adapted to respond to a laser pulse exiting from a breast being scanned; a multi-gain preamplifier circuit connected to the output of the photodetector; a switch connected to the output of the multi-gain preamplifier for sampling the output of the photodetector; an RC circuit for spreading the sampled signal; an amplifier connected to the output of the RC circuit; and an integrator for integrating each sample of the output. A time-gating circuit is operably connected to the switch to open and close the switch at regular intervals of time during the occurrence of the output. A laser pulse synchronization circuit is operably connected to the time-gating circuit to provide a signal to the time-gating circuit as to when the laser pulse is expected to arrive at the photodetector.

RELATED APPLICATION

[0001] This divisional application claims the priority benefit ofapplication Ser. No. 09/199,440, filed Nov. 25, 1998, which claims thepriority benefit of provisional application serial No. 60/066,479, filedNov. 26, 1997.

FIELD OF THE INVENTION

[0002] The present invention relates generally to a diagnostic medicalimaging apparatus and more particularly to a mammography machine thatemploys a near-infrared laser as a radiation source.

BACKGROUND OF THE INVENTION

[0003] Cancer of the breast is a major cause of death among the Americanfemale population. Effective treatment of this disease is most readilyaccomplished following early detection of malignant tumors. Majorefforts are presently underway to provide mass screening of thepopulation for symptoms of breast tumors. Such screening efforts willrequire sophisticated, automated equipment to reliably accomplish thedetection process.

[0004] The x-ray absorption density resolution of present photographicx-ray methods is insufficient to provide reliably early detection ofmalignant tumors. Research has indicated that the probability ofmetastasis increases sharply for breast tumors over 1 cm in size. Tumorsof this size rarely produce sufficient contrast in mammogram to bedetectable. To produce detectable contrast in photographic mammogram,2-3 cm dimensions are required. Calcium deposits used for inferentialdetection of tumors in conventional mammography also appear to beassociated with tumors of large size. For these reasons, photographicmammography has been relatively ineffective in the detection of thiscondition.

[0005] Most mammographic apparatus in use today in clinics and hospitalsrequire breast compression techniques which are uncomfortable at bestand in many cases painful to the patient. In addition, x-rays constituteionizing radiation which injects a further risk factor into the use ofmammographic techniques as most universally employed.

[0006] Ultrasound has also been suggested, as in U.S. Pat. No.4,075,883, which requires that the breast be immersed in a fluid-filledscanning chamber. U.S. Pat. No. 3,973,126 also requires that the breastbe immersed in a fluid-filled chamber for an x-ray scanning technique.

[0007] U.S. Pat. No. 5,692,511 discloses a laser imaging apparatus.

[0008] In recent times, the use of light and more specifically laserlight to non-invasively peer inside the body to reveal the interiorstructure has been investigated. This technique is called opticalimaging. Optical imaging and spectroscopy are key components of opticaltomography. Rapid progress over the past decade have brought opticaltomography to the brink of clinical usefulness. Optical wavelengthphotons do not penetrate in vivo tissue in a straight line as do x-rayphotons. This phenomena causes the light photons to scatter inside thetissue before the photons emerge out of the scanned sample.

[0009] Because x-ray photon propagation is essentially straight-line,relatively straight forward techniques based on the Radon transform havebeen devised to produce computed tomography images through use ofcomputer algorithms. Multiple measurements are made through 360° aroundthe scanned object. These measurements, known as projections, are usedto backproject the data to create an image representative of theinterior of the scanned object.

[0010] In optical tomography, mathematical formulas and projectiontechniques have been devised to perform a reconstruction functionsomewhat similar to x-ray tomography. However, because light photonpropagation is not straight-line, techniques to produce cross-sectionimages are mathematically intensive and invariably require establishingthe boundary of the scanned object. Boundary determination is importantbecause it serves as the basis for reconstruction techniques to produceinterior structure details. Algorithms to date do not use any form ofdirect measurement technique to establish the boundary of the scannedobject.

[0011] Photon propagation through breast tissue does not follow astraight line and can best described as “drunkard's walk”. The mean freepath of a photon within the breast is on the order of 1 mm, and afterthis short distance the photon is deflected at a different direction. Ingeneral, the photons are said to be forward scattered with the mean ofthe cosine of the scattering angle on the order of 0.9. The index ofrefraction of breast tissue is approximately 1.5 and thus the speed ofphoton travel within the breast is on the order of 2×10⁸ meters persecond.

[0012] In accordance with the present invention, knowledge of thepropagation of light through the breast tissue, determination of theperimeter of the breast at the selected scanning location, and the knownconfiguration of the scanner allow a method of selecting those photonsthat travel the shortest path through the breast to be used to produce acomputed tomography of the interior of the breast.

OBJECTS AND SUMMARY OF THE INVENTION

[0013] It is an object of the present invention to provide a detectorarray that can detect the significantly different light levels emergingfrom a scanned object.

[0014] It is another object of the present invention to provide aprocessing circuit for a detector that can accommodate the dynamic rangeof the detector.

[0015] It is still another object of the present invention to provide adetector with multiple gain amplifier to accommodate the dynamic rangeof the detector signal, which could range in relative amplitude fromapproximately 10⁻¹¹ to 1.

[0016] It is another object of the present invention to provide aprocessing circuit that can detect the earliest arriving photons exitingfrom the breast being scanned.

[0017] It is another object of the present invention to acquire data toallow reconstruction of contiguous cross-section images of the interiorof a breast using short pulses of near infrared light.

[0018] It is an object of the present invention to provide a directdetermination of the boundary of the scanned object, thus eliminating asignificant portion of the time required to reconstruct an interiorimage of the scanned object.

[0019] It is another object of the present invention to provide one ormore sensors placed on the same side of the scanned object as theimpinging radiation to detect the location of the point of contact ofthe impinging beam on the scanned object and using this information todetermine the boundary of the object.

[0020] It is another object of the present invention to provide a meansfor directing a laser beam into the breast by use of a fiber optic cableand to couple light collected by a collimator to a photodetector.

[0021] It is another object of the present invention to provide a meansby synchronizing the data acquisition circuits to the arrival of photonsdelivered through fiber optic cable and optics.

[0022] It is another objective of the present invention to provideprocessing circuit to allow acquiring data to determine the TPSF foreach scan location, and use the TPSF to estimate the transportscattering coefficient, μ_(s)′, and the absorption coefficient, μ_(a).

[0023] It is still another objective of the present invention to providedata for imaging reconstruction through use of all or time-gatedportions of the TPSF data.

[0024] In summary, the present invention provides a detector array for alaser imaging apparatus, comprising a plurality of detectors disposed inan arc around an opening in which an object to be scanned is disposed;and a multi-gain amplifier circuit connected to each detector.

[0025] The present invention also provides a detector array for a laserimaging apparatus, comprising a plurality of detectors disposed in anarc around an opening in which an object to be scanned is disposed; anda multi-gain amplifier circuit means for processing the output of eachdetector to provide data for use in image reconstruction.

[0026] The present invention further provides a photodetection circuitfor use in a laser imaging apparatus, comprising a photodetector adaptedto respond to a laser pulse exiting from a breast being scanned; amulti-gain preamplifier circuit connected to the output of thephotodetector; a switch connected to the output of the multi-gainpreamplifier for sampling the output of the photodetector; an RC circuitfor spreading the sampled signal; an amplifier connected to the outputof the RC circuit; and an integrator for integrating each sample of theoutput. A time-gating circuit is operably connected to the switch toopen and close the switch at regular intervals of time during theoccurrence of the output. A laser pulse synchronization circuit isoperably connected to the time-gating circuit to provide a signal to thetime-gating circuit as to when the laser pulse is expected to arrive atthe photodetector.

[0027] The present invention still provides a method for collecting datafor use in image reconstruction of an object being scanned, comprisingproviding a plurality of detectors disposed in an arc around the objectto be scanned; connecting a multi-gain amplifier circuit to eachdetector; impinging a laser beam at a point on the object; sampling theoutput curve of each detector in sufficient time intervals to recreatethe curve; integrating each sample; repeating the sampling andintegrating for a number of laser pulses; recording each output for eachpulse for use in image reconstruction; orbiting the detectors and thelaser beam to another point on a circle; and repeating the above until acomplete circle has been traversed.

[0028] The present invention also provides an apparatus for determiningthe perimeter of an object being scanned, comprising a scanning chamberfor receiving therein an object being scanned; a source of laser beamdisposed within said scanning chamber for impinging on the object beingscanned, said laser beam being adapted to orbit around the object; anarray of sensors disposed within said chamber, each of said sensorsbeing adapted to detect light reflecting from the surface of the objectdue to said laser beam exiting from the object; each of said sensorsbeing disposed such that at least only one of said sensors generates apeak response to light emanating from a point on the surface at apredetermined distance from a reference point, such that at each angularposition of said laser beam in the orbit, a specific point at a distancefrom the reference is determined, thereby to generate a set of pointsrepresenting the perimeter of the surface after a complete orbit.

[0029] These and other objectives of the present invention will becomeapparent from the following detailed description.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[0030]FIG. 1 is a schematic side elevational view of an optical imagingapparatus made in accordance with the present invention, showing apatient on a support platform with one of her breasts positioned withina scanning chamber configured to exclude ambient light.

[0031]FIG. 2 is a schematic top view of a scanning chamber, showing thegeometrical relationships between a laser beam, an array ofphotodetector assemblies and an arrangement for determining theperimeter of an object being scanned.

[0032]FIG. 3 is a block diagram of the signal processing system used inthe present invention.

[0033]FIG. 4 is a schematic top view of the scanning chamber of FIG. 1,showing the geometric relationships between the impinging laser beam,chord paths through the object and the detector assemblies.

[0034]FIG. 5 is a graph of the relationship of the relative amplitude ofdetector signal and its corresponding chord path length through theobject being scanned.

[0035]FIG. 6 is a detector assembly used in the present invention.

[0036]FIG. 7 is a graph of detector sensitivity relative to itsgeometric location for the scanner of FIG. 2 having 84 detectors.

[0037]FIG. 8 is a schematic diagram of the scanning apparatus of FIG. 1.

[0038]FIG. 9A is a representation of a propagating laser pulse through anon-attenuating medium.

[0039]FIG. 9B is a representation of various paths, called photon bananapaths, the laser pulse takes traveling through the breast.

[0040]FIG. 10 is a response curve of a high-speed photodetectorilluminated by a laser pulse after that has traveled through the breast.

[0041]FIG. 11 is a schematic diagram of photodetector circuit used inthe present invention.

[0042]FIGS. 12A and 12B are schematic representations of the time oftravel for a laser pulse going through the breast and a synchronizationpulse going through a parallel path.

[0043]FIG. 13 is shows the relative electronic signals in the scanner.

[0044]FIG. 14 is a schematic diagram of a processing system for thephotodetector signal, showing three amplification stages to accommodatethe dynamic range of the detector output.

[0045]FIG. 15 is a schematic diagram of a monolithic microwaveintegrated circuit amplifier used in the present invention.

[0046]FIGS. 16A, 16B, 16C and 16D are a schematic diagram of a RCcircuit used in the present invention and the associated waveforms.

[0047]FIG. 17 is another embodiment of a processing circuit foramplifying the output of the photodector.

[0048]FIG. 18 is another embodiment of a processing circuit foramplifying the output of the photodetector.

[0049]FIG. 19 is a schematic diagram of a high-speed switch used in thepresent invention.

[0050]FIG. 20 is a block diagram of a programmable delay chip used inthe present invention.

[0051]FIG. 21 is a block diagram of a plurality of programmable delaychips cascaded together for increased number of delay intervals.

[0052]FIGS. 22A, 22B, 22C, 22D and 22E shows the extent of the TPSFcurve that is sampled using successively longer time-gate period.

[0053]FIG. 23 is a block diagram of a laser system used in the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

[0054] A scanning apparatus 2, such as that described in U.S. Pat. No.5,692,511, which is hereby incorporated by reference, is schematicallydisclosed in FIG. 1. A patient 4 is positioned prone on a top surface ofthe apparatus 2 with her breast 6 pendent within a scanning chamber 8configured to exclude ambient light. A laser beam from a laser source 10is operably associated with the scanning chamber 8 to illuminate thebreast 6.

[0055] The scanning chamber 8 includes a scanner 9 and is shownschematically in plan view in FIG. 2. The scanning chamber includes aplurality of detector assemblies 12 disposed in an arc to define anopening in which an object 14 to be scanned, such as the breast, ispositioned. A laser beam 16 impinges the object at point 18. Lightexiting from the object 14, such as the rays 20, is picked up by therespective detector assemblies 12, that is then used to provide an imageof the scanned object. The rays 20 are assumed to take the pathsrepresented by chords originating from the point of entry 18 of thelaser beam 16 and exiting at various points on the perimeter 19 of thescanned object.

[0056] The detector assemblies 12 are digitally orbited around theobject 14 about an orbit center 22 at equal angular increments for atotal angular displacement of 360° in a direction generally indicated at23. The object 14 is illuminated with the laser beam 16 at each angularposition in the orbit 23. The light emerging from the object depicted bythe chords 20 on the perimeter of the scanned object, at one instant intime or in a period of time acquired simultaneously, is picked up by therespective detector assemblies 12. Each detector assembly has itslongitudinal axis directed toward the orbit center 22. The detectorassemblies 12 are secured to a support 36, which is orbited in orbit 23around the object 14 being scanned.

[0057] After each complete orbit, the array of detector assemblies 12and the laser beam 16 are moved vertically to a new position to scan adifferent slice plane of the object. This is repeated until all theslice planes of the object has been scanned.

[0058] Each detector assembly 12 includes an opaque housing 24 with anopen front end 26 and a rear end 28 in which a detector 30 is disposed.Preferably, each detector 30 is disposed remotely from the housing 24 bymeans of a fiber optic cable that connects the respective detector tothe respective housing (see FIG. 6), as will be discussed below. Theinside surface of the housing 24 can be tubular, round, square or othercross-sectional shape. The housing 24 is designed to restrict the fieldof view of its respective detector 30, such that each detector is onlylooking at its own small area of the scanned object. The field of viewof each detector assembly 12 is schematically indicated at 32. A patchor surface seen on the scanned object by the respective detectorassembly is schematically indicated at 34.

[0059] The field of view 32 and the respective patch of surface 34 areconfigured such that adjacent patches of surface minimally overlap eachother. In this way, each detector assembly is uniquely assigned to apatch of surface at each angular position of the orbit so that lightcoming from one patch of surface could only be detected by therespective detector whose field of view covers that particular patch ofsurface. Each detector 30 is active to detect any light emerging fromits respective patch of surface, since the light beam 16 can coursethrough the object in any paths, such as those depicted by the chords20. Each housing is further described in copending application Ser. No.08/963,760 filed Nov. 4, 1997, claiming priority based on provisionalapplications serial Nos. 60/032,591, 60/032,592 and 60/032,593, allfiled on Nov. 29, 1996, all of which are hereby incorporated byreference.

[0060] Each detector or sensor 30 is operably connected to itsrespective processing circuit 40, as best shown in FIG. 3. A multiplexer42 is used to connect the respective integrator outputs to ananalog-to-digital converter 44. The digitized individual detector orsensor response is stored in memory 46 for later use in imagereconstruction by a computer 47. The circuit allows for simultaneousacquisition of data from all the detectors 30 at each angular positionin the orbit of the scanning chamber 8. An example of the circuit 40 isfurther described in a copending application Ser. No. 08/979,328 filedon Nov. 26, 1997, claiming priority based on provisional applicationserial No. 60/032,590, filed on Nov. 29, 1996, both of which are herebyincorporated by reference. An improved embodiment of the circuit 40 willbe discussed below.

[0061] Perimeter data of the object being scanned is obtained at eachangular position in the orbit of the scanning chamber 8. Several methodsare disclosed in copending application Ser. No. 08/965,148 filed on Nov.6, 1997, claiming priority from provisional applications serial Nos.60/029,897 and 60/029898 both filed on Nov. 8, 1996 and application Ser.No. 08/965,149 filed on Nov. 6, 1997, claiming priority from provisionalapplication serial No. 60/029,898 filed Nov. 8, 1996, all of which arehereby incorporated by reference.

[0062] Preferably, a pair of sensor arrays 49 and lens 51 are disposedon the same side as the laser beam 16, as best shown in FIG. 2. Thelaser beam 16 impinges on the scanned object through the center 22 ofthe orbit. A bright spot is produced at point 18, which is reflected tothe sensor arrays 49, represented by lines 53. At each distance from theorbit center, a specific element in the sensor array 49 will detect thebright spot. As the laser beam 16 and the rest of the scanner areorbited around the scanned object about the center, the output signal ofthe sensor array 49 will be in direct relationship to the perimeter ofthe scanned object. By acquiring data using one or more known diametersscanned objects, the level of the sensor signal can be calibrated withrespect to the scanned object diameters. After calibration, the sensorsignal can be electronically decoded to plot the coordinates for theperimeter of the scanned object as the scanner is orbited around thescanned object.

[0063] Each of the sensors 49 is a CCD sensor, such as CCD televisionpick up device, available from Texas Instruments, EG&G and others, andincludes lenses 51 to focus the rays 51 to the sensors. For the presentinvention, the sensor 49 is a linear, one dimensional CCD device, ratherthan the area 2-dimensional array used for television. The CCD sensorproduces an analog signal corresponding to the light received along theline. A processing circuit 55 (shown in FIG. 8) can be implemented as ananalog circuit, a digital hardware or in software running on aprogrammable device. An ADC (analog-to-digital converter) digitizes thevideo signal prior to processing by the computer.

[0064] It is advantageous to obtain the perimeter data during datacollection of each slice to minimize error due to shifting of the objectbetween slice positions. Perimeter data is used to calculate the chordlengths 20, which together with the corresponding detector data are usedto reconstruct the image of the object. With the perimeter data, thechord lengths 20 at each scan position of the scanner 9 are known.Perimeter data consist of distances from the center of the orbit 22 tothe point 18 at each angular position of the orbit.

[0065] The scanner 9 is represented schematically in FIG. 4. Thedetectors 30 are designated as AA, BB, . . . , KK, indicating theirrespective positions along the arc. Optical path lengths taken by thelaser beam through the object are represented as chords 18-A, 18-B, . .. , 18-K. At each angular position in the orbit 23, the relativeamplitude of the detector signals at the detectors AA, BB, . . . , KKare generally indicated by the curve 48 shown in FIG. 5. The signalsseen by the detectors AA and KK are strongest because of the shorterchord lengths 18-A and 18-K. The signal seen by the detector FF issmaller because of its corresponding longer chord length 18-F. It istherefore seen that the signal generally decreases from detectors AA toFF and increases from detectors FF to KK. Detector signal beforeamplication can range from 10⁻¹⁰ to 1 in relative amplitude.

[0066] A preferred embodiment of the detector assembly 12 is disclosedin FIG. 6. A plano-convex lens 52 disposed within the housing 24 focusesthe light unto a ball lens 54 which launches the light rays into a fiberoptic cable 56. At the far end of the optic cable 56 is anotherplano-convex lens 58, which may be integral with the photodetector 30disposed within an opaque housing 60. The fiber optic cable 56 issufficiently long such that the detector 30 and its associatedprocessing circuit 40 may be located remotely from the scanning chamber8 and be sufficiently spaced from other detectors 30 to preventelectronic interference from each other.

[0067] In the present invention, 84 detector assemblies are used,although a different number is possible. The signal seen by each of thedetector 30, depending on the physical location of housing 24 in thescanner 8, can vary approximately from 10⁻¹⁰ to 1.0 in relativeamplitude. To accommodate this wide range, each detector assembly 12 isgraded in terms of efficiencies and those with the highest efficiencyare placed in the center of the detector array, such as detectorposition FF, with the longest path length through the breast and lowerefficiencies assemblies are positioned where shorter optical pathlengths through the breast are expected, such as detector position AA,as best shown in FIG. 7. With knowledge of the relative signal strengthsas a function of location in the detector housing array and efficiencyof the individual detector assemblies, the positioning of the detectorassemblies 12 is implemented to use the highest efficiencies assemblieswhere the signal can reasonably be expected to be small.

[0068] The scanning apparatus 2 is disclosed schematically in FIG. 8.The output of the laser source 10 is a laser beam 62 directed to a beamsplitter 64 to provide a laser beam 66 directed to a fiber optic cable68 and another laser beam 70 directed to another fiber optic cable 72.The laser beam 66 as it emerges from the optic cable 68 is directed toanother beam splitter 74 and emerges as a reduced power laser beam 16,and is directed into a lens collimator 78 (see FIG. 2). The lenscollimator 78 controls the beam diameter of the laser beam 16. Thesecond beam 80 from the beam splitter 74 is directed to a powermonitoring diode 82 connected to a power monitoring circuit 84, using anamplifier and an analog-to-digital converter to produce a digital signalrepresenting the power level of the laser beam 16. The laser beam 16impinging on the breast 6 travels as optical chords 20 through thebreast 6 and emerges at various locations 34 on the perimeter 19 of thebreast, as best shown in FIG. 2. The housings 24 are optical collimatorsthat limit the field of view to corresponding locations 34 on theperimeter of the breast 6. The light that enters each of the housings 24is transmitted through the fiber optic cable 56 and impinges on thedetector 30 at the other end of the fiber optic cable 56.

[0069] Each of the detectors 30 is coupled to the sample and holdintegrator circuit 40, the output of which is coupled to the multiplexer42, which is connected to the analog-to-digital converter 44, and whichis connected to the computer 47.

[0070] The laser beam 70 emerging from the fiber optic cable 72 iscoupled to a photo-detector 102, which develops a signal used by a lasersynchronization circuit 104, which generates an electronic pulse eachtime the laser source 10 produces a pulse of power. The arrival time ofthe laser pulse at the detector 102 and hence the time at which thelaser synchronization pulse is generated is controlled by the length ofthe fiber optic cable 72. Fine tuning of the time of occurrence of thelaser synchronization pulse is provided by a time delay circuit 106,which produces a delayed signal. The time delay circuit 106 may beimplemented with a few feet of cable. The time delay lasersynchronization pulse is used as one input to a high speed time-gatedelectronic switch control circuit 108. The computer 47 also provides adelay control signal to the control circuit 108. A laser pulse counter110 is controlled by the computer 47 to provide a signal to the circuit40 to control the integration time that occurs within the circuit, aswill be further discussed below.

[0071] Referring to FIG. 9A, a laser pulse propagating through anon-attenuating medium such as air will travel in a straight line. Alaser pulse directed into a breast does not follow a straight-linepropagation path, best shown in FIG. 9B. Breast tissue causes the photonbeam to scatter, resulting in a zig-zag-like course through the breast.The zig-zag-like course in 2- or 3- dimensional space is referred to asa banana path. Referring to FIG. 9, square wave laser pulse aftertraversing through the breast will emerge with a general shape shown.Because all of the photons do not follow the same path, the measuredphoton intensity at the measurement point on the surface of the breastis time dependent. A small number of photons arrives first, followed byphotons that have traveled a longer path, and lastly followed by thephotons that have taken the longest path through the breast. The earlyarriving photons are used in image reconstruction.

[0072] A detector with high-speed response characteristics can be usedto display the photon-intensity versus time plot, called the TemporalPoint Spread Function (TPSF) curve, of a laser pulse transmitted throughthe breast. A TPSF curve of a laser migrating through a media isdisclosed in FIG. 10. The TPSF curve can be fitted to the diffusionequation. After curve fitting, the diffusion equation can be used todetermine the optical characteristics of the breast, such as theabsorption coefficient, μ_(a), the transport scattering coefficient,μ_(s)′, and the index of refraction, η, can be calculated. Portion 111of the curve represents photons that are among the earliest to emergefrom the breast and thus have undergone the least amount of scattering.The earliest arriving photons represented by the portion 111 of thecurve are used in image reconstruction. Portion 113 represents photonsthat are highly scattered and are not used in image reconstruction.

[0073] For a detector circuit having response characteristics shown inFIG. 10, its rise-time, the time required for the amplitude starting at10% peak value to reach its 90% peak value, is approximately 300picoseconds (ps). From this, the approximate bandwidth of the detectorcircuit would be 0.35/300 ps or 1.2 GHz.

[0074] In a detector circuit 112 used in the present invention, as shownin FIG. 11, the photodetector 30 is reversed biased to reduce thephoto-diode capacitance, represented by capacitor 114. Capacitor 116decouples the photo-diode 30 from the bias supply. Current flow in thediode 30 begins a few picoseconds after the photons begins impinging onthe photo-diode. The combined capacitance, comprising of the junctioncapacitance, package capacitance and stray wiring capacitance, and theload resistance 118 determine the rise-time of the overall circuit. Forhigh frequency applications, the load 118 is preferably 50 ohms. For aphoto-diode with a capacitance of 1 pf, the rise-time is calculated asfollows,

t _(r)=2.2R _(L) C _(d)=2.2(50 ohms)(1×10⁻¹² f)=110 ps

[0075] The approximate frequency response of the photo-diode circuit is,

0.35/110×10⁻¹²=3.2 GHz.

[0076] High speed photodetectors with a capability to capture thewaveform of a fast light-pulse, such as that shown in FIG. 10, areavailable today. Advances in photo-detector technology have producedphotodetectors with small size active areas resulting in lowcapacitance.

[0077] The propagation of a laser pulse through the scanning apparatus 2will now be described. The point in time at which the laser pulse willarrive at the detector 30 after passing through the breast can becalculated. Referring to FIG. 12A, in a path starting at the beamsplitter 64 and going through the fiber optic cable 68, distances that alaser pulse would traverse up to the point it exists the breast areknown, indicated as d₁, d₂, d₃, d₄ and d₅. The distance d₄ is known fromthe perimeter data of the breast. The corresponding time periods t₁, t₂,t₃, t₄ and t₅ can be calculated from the known distances and the knownspeed of light in air, the fiber optic cable 68 and the breast. Thespeed of propagation of the laser pulse through the breast can beapproximated. The nominal value of the index of refraction, η, of thebreast tissue is 1.54. The speed of light in the breast, c_(b), can becalculated as follows,

c _(b)=speed of light in a vacuum/η, index of refraction,

c _(b)=3×10⁸ m/s/1.5=2×10⁸ m/s.

[0078] With the chord length having been determined previously from theperimeter data, then the time of propagation t₄ through the breast is,

t ₄=chord length/c_(b).

[0079] The laser pulse as it emerges from the breast will then travelthrough the fiber optic cable 56 and then impinge on the detector 30.The known distance of the fiber optic cable 56 is d₅ and thecorresponding time of travel through it is t₅. The duration length ofthe TPSF curve is indicated as t_(pt).

[0080] The time of propagation t₆ of the laser pulse from the beamsplitter 64 through the fiber optic cable 72 can be calculated from theknown length d₆ of the cable 72. The time t₆ can be adjusted bylengthening the fiber optic cable 72 to delay the arrival of the laserpulse at the photodetector 102 or by shortening the length of the fiberoptic cable 72 to shorten the arrival time. The time t₆ is configured tobe just short of the time for the laser pulse to reach the detector 30,as best shown in FIG. 12B.

[0081] The output of the photodetector 102 is used by the lasersynchronization circuit 104 to generate a pulse each time a laser pulseis detected by the photodetector 102. The time at which thesynchronization pulse is generated may be fine tuned by an amount t_(ft)by the time delay circuit 106, which generates a delayed pulse. Thelaser synchronization pulse is used as one input to the high speedtime-gated electronic switch control circuit 108. The output of thecircuit 108 is controlled by the computer 47.

[0082] The time-gating signal of the circuit 108 is adjustedapproximately in 17 picosecond increments over approximately a 17nanosecond period, which is approximately the width of the TPSF curve.Referring to FIG. 12B, the expected arrival of the laser pulse at thedetector 30 is t_(a), using t=0 starting at the beam splitter 64. Theexpected time of arrival of the synchronization laser pulse at detector102 is t₆. The time delay circuit 106 introduces a time delay to finetune the synchronization pulse at t_(ft), which is just before timet_(a). The time period t_(g) for sampling the TPSF curve starts justbefore the beginning of t_(pt) and after the end of t_(pt), thusbracketing the duration length of the TPSF curve.

[0083] Referring to FIG. 13, the relative electronic timing of signalsis disclosed. The laser beam 70 propagating through the fiber opticcable 72 includes laser pulses 120 which generate a signal 122 at thelaser synchronization detector 102. The synchronization circuit 104generates a signal 124, which causes the time delay 106 to generate thetime delayed signal 126. The signal 126 initiates a time-gating signal128, which is adjusted in approximately 17 picoseconds overapproximately a 17 nanosecond period by means of a programmable delaychip controlled by the computer 47, as will be discussed below. Thetime-gating signal 128 samples a portion of the TPSF curve that will becoupled to an integrator in the circuit 40. The input to the integratoris the selected portion of the TPSF curve. The integrator generates asignal 130. The integrator is also controlled by a hold signal 132 and areset signal 134.

[0084] A schematic diagram of the signal processing circuit 40 isdisclosed in FIG. 14. The circuit 40 provides three different amplitudesfor the detector signal of detector 30. The output of each highfrequency linear pre-amplifier 136 is coupled to high speed time-gatedelectronic switch 140, RC network 142, an amplifier 144 and anintegrator 146. The integrator 146 includes a hold switch 145 and areset switch 147.

[0085] The circuit 40 is configured to have a low-gain stage 148, amedium-gain stage 150 and a high-gain stage 152. The three gain stagesare designed to accommodate the large dynamic range of detector signalsavailable for detection that can range from 10⁻¹⁰ to 1 in relativeamplitude.

[0086] A high speed electronic switch 153 is advantageously used todisconnect the power to the pre-amplifiers 136 and the high speedtime-gated electronic switches 140 to achieve a substantial reduction inthe amount of power used by the circuit between laser pulses.

[0087] The high frequency linear pre-amplifier 136 is known as amonolithic microwave integrated circuit (MMIC), which is a radiofrequency amplifier specifically designed to have exceptionalperformance at high RF frequencies. The MMIC 136 itself is a singlecomponent with four electronic connections; namely, an input terminal,an output terminal and two ground connections, as best shown in FIG. 15.An input capacitor 154 is used to AC couple an input signal to the MMIC.An output capacitor 156 is used to AC couple the amplified output signalto the next stage of the circuit. Resistor 158 is used to set theoperating points for the device by producing a voltage drop to establisha DC voltage at the output terminal of the MMIC. A choke 160 is used todecouple the resistor 158 from the MMIC. The capacitors 154 and 156 arecritical to optimal circuit performance of the MMIC. At GHz frequenciesat which the MMIC operates, microwave capacitor with packageconstruction that minimizes lead-inductance must be used. The MMIC's areselected for the gain they produce and their useful operating frequencyrange. MMIC's are available from Mini-Circuits, models ERA-1 and ERA-5,which are used in the present invention.

[0088] Referring to FIGS. 16A, 16B, 16C and 16D, the RC filter 142stretches the width of a sampled signal 155 to produce a stretchedsignal 157 which is then amplified by the amplifier 144 to produce anamplified signal 159 to allow the integrator 146 to produce a largerdetector signal. Since time gating has controlled the sampling of thesignal 155, stretching the width of the signal 155 after sampling tobecome signal 157 followed by the amplifier 144 does not defeat thesampling process but provides a wider window of time for the integrator146 to integrate. The stretching feature is a key function thatadvantageously allows fewer laser pulses to be used for any onemeasurement and advantageously reduces the time required to perform ascan.

[0089] Another embodiment for the circuit 40 is disclosed in FIG. 17 ascircuit 162. The output of each detector 30 is directly connected tothree gain stages, namely, a low-gain stage 164, a medium-gain stage 166and a high-gain stage 168. Samples switches 140 are individuallycontrolled.

[0090] A preferred embodiment of the signal processing circuit 40 iscircuit 176, as best shown in FIG. 18. The circuit 176 has a high-gainpre-amplifier stage 178, a medium-gain pre-amplifier 180 and a low-gainpre-amplifier stage 182. The high-gain pre-amplifier stage 178 consistsof three cascaded MMIC pre-amplifiers 136 with an overall gain equal tothe product of the gains of the respective MMIC's.

[0091] The overall gain of the low-gain pre-amplifier stage 182 is theproduct of the respective gains of the two MMIC pre-amplifiers 136 andthe attenuation provided by the resistive circuit 184. The overall gainis set to one.

[0092] The overall gain for the medium-gain pre-amplifier stage 180 isthe product of the gains of the three respective MMIC pre-amplifiers 136and the attenuation provided by the resistive circuit 186. The values ofthe resistors in the resistive circuit 186 are chosen such that theoverall gain for the medium-gain pre-amplifier stage 180 is equivalentto the overall gain of two cascaded MMIC pre-amplifiers.

[0093] The sampling switch 140 is implemented as a diode-bridge switch190, as disclosed in FIG. 19. The diode-bridge switch 190 switches at avery high speed to accommodate the 17 picoseconds sampling intervals.However, the switch produces a switching transient signal and DC offsetthat appears as an input signal on the output of the MMIC providing thedesired signal to the bridge. In the preferred circuit 176, thereflected signal from the switch 190 is advantageously attenuated as itpasses through the MMIC pre-amplifiers 136 in the low and high mediumpre-amplifier stages 180 and 182 and by the 50-ohm characteristics inputimpedance of the MMIC and the resistive circuits 184 and 186. Thereflected signal is undesirable, since the reflected signal can belarger than some detector signals.

[0094] In the circuit 168, the transient reflected signal from thediode-bridge switch appears as an input to high-gain pre-amplifier stage168. Although the reflected signal is attenuated by approximately afactor of 10, it is amplified by approximately a factor of 10³ by thethree cascaded MMIC pre-amplifiers 136. The DC offset of the reflectedsignal causes the high-gain pre-amplifier stage integrator 140 torapidly integrate to one power supply rail.

[0095] Referring back to FIG. 19, the switch 190 includes a diode bridgecircuit 191, commonly used as a RF switch to sample a (temporal) portionof a waveform, as in a sampling oscilloscope. The diode bridge circuit191 is turned on and off by voltage sources at line 193 and 195, actingrespectively through diodes 194 and 197. To close the switch, thevoltage at line 193 would be at a positive voltage, backbiasing diode194 and the voltage at line 195 at a negative voltage, backbiasing thediode 197. Thus, all the bridge diodes will be conducting and the signalat the input IN will appear at the output OUT.

[0096] With the voltage at line 193 at a negative voltage and thevoltage at line 195 at a positive voltage, diodes 196 and 198 will bebackbiased, isolating the output OUT from the input IN. Typically, thevoltages at lines 193 and 195 will be mirror-image waveforms.

[0097] The voltages at lines 193 and 195 are provided by the signalsSAM, which are differentials ECL, normally false. Thus, transistor 199is normally on and transistor 200 is off. The bias voltages 201 and 202are set to be slightly larger than the largest input signal, butsignificantly smaller than voltages 203 and 205. The diode bridgecircuit 191 is normally off with the diodes 194 and 197 conducting.

[0098] To sample the input, SAM+ is driven high and SAM− is driven lowsimultaneously. Transistor 200 turns on and transistor 199 turns off.Coupled through capacitors 207 and 209, diodes 194 and 197 are driven toa backbiased state. The diode bridge circuit 191 now conducts the inputto the output.

[0099] The electronic switch control circuit 108 is implemented by aprogrammable delay chip 192, as best shown in FIG. 20. The programmabledelay chip 192 is made by Motorola, model no. MC10E195-MC100E195. ModelNo. MC10E196-MC100E196 can also be used. The programmable delay chip 192is designed to produce a series of delays 17 picoseconds apart. Severalprogrammable delay chips 192 may be cascaded to provide the requiredtime delays, as best shown in FIG. 21. The present invention uses eightprogrammable delay chips to sample the entire TPSF curve atapproximately 17 picosecond intervals. This will provide 1024 samplingsteps for a TPSF curve as long as 17 ns for the longest expected chordlength through a large breast.

[0100] The portion of the TPSF data that is sampled in the t_(g)interval is selectable at approximately 17 picoseconds steps over a 17nanosecond window. Preferably, the sampling intervals are 8 blocks of 17ps intervals.

[0101] Electronic control of the delay time is provided by theprogrammable delay chip 192. Since the detector signals are small,multiple laser pulses, preferably 5, are used to develop a largersignal. Three different numbers of laser counts are used to develop anever increasing signal, since there is no way of knowing the amplitudeof the signal that would be experienced. Thus, for any one time-gateinterval, groups of 8, 16 and 32 laser pulses might be collected. Thelaser pulse numbers can be set in interval values ranging from 1 to 128pulses. After a preset number of laser pulses has been sampled, the nexttime-gate is set to sample along the portion of the TPSF curve. Thelength of the TPSF curve is also not known and actually changes asdifferent portions of the breast are scanned. A longer chord through thebreast produces a longer TPSF curve with a decreasing leading edge time.The time delay intervals and the total width of the period of timerequired to capture the entire TPSF is not known ahead of time. Thelaser-pulse counting and incrementing of the time-gate delay is repeateduntil the available range of values has been covered. The result of thisform of data collection is to attempt to acquire data that will cover aconsiderable number of variables that are encountered in actual in-vivoscanning. For example, one acquired data contains approximately 16 megabytes of data.

[0102] The computer 47 sets the time-gate delay signal to select howmuch of the TPSF data will be used. A computer command sets the numberof laser pulses that would be used by the integrator 146. The laserpulse counter is incremented by each laser synchronization pulsegenerated by the circuit 104. The number of laser pulses that will beused is set into the laser pulse counter 110 by the computer 47.

[0103] FIGS. 22A-22E illustrate the sampling of a TPSF curve as thetime-gate delay t_(g) is incremented to progressively sample the curve.Since t_(a) is known (see FIG. 12B), the high speed time-gatedelectronic switch 140 is electronically closed at a time precedingt_(a). The time the high speed time-gated electronic switch 140 iselectronically closed is determined by the computer 47 and the circuit108. This technique advantageously detects photons that are among theearliest to emerge from the breast and thus has undergone the leastamount of scattering. The early arriving photons are used in imagereconstruction described in copending application Ser. No. 08/979,624,claiming priority from provisional application serial No. 60/032,594,filed on Nov. 29, 1996, both of which are hereby incorporated byreference.

[0104] The characteristics of the laser beam used in the presentinvention are important. Theoretical calculations and physicalexperiments have confirmed that at 790-800 nm wavelength range, a 3 mmdiameter, 500 milliwatt average power, P_(avg), laser beam with a pulsewidth, PW, of 110 femtosecond (fs) at a repetition rate, RR, of 82 MHzcauses no biological damage.

[0105] The power per square centimeter, P_(cm2) is calculated as:

Area of beam=ΠR ²=Π(3/2 mm)²=0.0706 cm²

[0106] $\begin{matrix}{P_{cm2} = {\left( {{1/0.0707}\quad {cm}^{2}} \right) \times 500\quad {mW}}} \\{= {7.07\quad {W/{cm}^{2}}}}\end{matrix}$

[0107] The energy per pulse, E_(pp) is calculated as: $\begin{matrix}{{Epp} = \quad {{P_{avg}/{RR}} = {500\quad {{mW}/8.2} \times 10^{7}}}} \\{= \quad {6.095 \times 10^{- 9}\quad J}} \\{\approx \quad {6.1\quad {nJ}}}\end{matrix}$

[0108] The peak power, P_(p), is calculated as: $\begin{matrix}{P_{p} = {{E_{pp}/{PW}} = {6.1\quad {{nJ}/110}\quad {fs}}}} \\{= {6.1 \times {10^{- 9}/1.1} \times 10^{- 13}}} \\{= {{55,454.5\quad W} = {55.5\quad {kW}}}}\end{matrix}$

[0109] In the present invention, peak power per pulse is not ofsignificance, but energy per pulse is because energy per pulsedetermines the number of photons that are available for imaging. Thequantum energy of a photon, e, is calculated as follows:

e=hf

[0110] where h=6.6252×10⁻³⁴ Js, Planck's constant, and

f=the frequency=c/λ

[0111] where c=3×10⁸ meter per second and λ=800 nm $\begin{matrix}{e = {6.6252 \times 10^{- 34}\quad {Js} \times \left( {3 \times 10^{8}\quad {{m/s}/8} \times 10^{- 9}\quad m} \right)}} \\{= {2.48 \times 10^{- 18}\quad J\quad {per}\quad {photon}}}\end{matrix}$

[0112] The energy per pulse was calculated above as 6.097×10⁻⁹ J. Thenumber of photons per pulse is calculated as follows

Number of photons per pulse=energy per pulse/energy per photon$\begin{matrix}{\begin{matrix}{{Number}\quad {of}\quad {photons}} \\{{per}\quad {pulse}}\end{matrix} = \quad \frac{{energy}\quad {per}\quad {pulse}}{{energy}\quad {per}\quad {photon}}} \\{= \quad {6.1 \times 10^{- 9}\quad {J/2.48} \times 10^{- 18}\quad J}} \\{= \quad {2.44 \times 10^{10}}}\end{matrix}$

[0113] If an attenuation factor of 10⁸ or 10¹⁰ is considered, it isclear that few photons would be available for imaging, especially whenthe scattering of the photon beam is considered. It has beenexperimentally determined that the energy per pulse required for medicaloptical imaging is on the order of 100 to 500 μJ. The number of photonsper pulse is calculated as follows:

[0114] Number of photons per pulse=energy per pulse/energy per photon$\begin{matrix}{{\begin{matrix}{{Number}\quad {of}\quad {photons}} \\{{per}\quad {pulse}}\end{matrix} = \quad {{\frac{{energy}\quad {per}\quad {pulse}}{{energy}\quad {per}\quad {photon}}@100}\quad {\mu J}}},} \\{\begin{matrix}{{Number}\quad {of}\quad {photons}} \\{{per}\quad {pulse}}\end{matrix} = \quad {1 \times 10^{- 4}\quad {J/2.48} \times 10^{- 18}\quad J}} \\{= \quad {4.03 \times 10^{13}}} \\{{{@300}\quad {\mu J}}\quad} \\{\begin{matrix}{{Number}\quad {of}\quad {photons}} \\{{per}\quad {pulse}}\end{matrix} = \quad {3 \times 10^{- 4}\quad {J/2.48} \times 10^{- 18}\quad J}} \\{= \quad {1.2 \times 10^{14}}}\end{matrix}$

[0115] The repetition rate of the laser 10 must be low enough to preventadverse physiological reactions. If the average power is held constantand the energy is known, then the repetition rate can be calculated asfollows: $\begin{matrix}{{{@100}\quad {\mu J}},{{RR} = \quad {P_{avg}/E_{pp}}}} \\{= \quad {{500\quad {{mW}/100}\quad {\mu J}} = {0.5\quad {W/1} \times 10^{- 4}\quad J}}} \\{= \quad {5,000\quad {pulses}\quad {per}\quad {second}}} \\{= \quad {5\quad {kHz}}} \\{{{@300}\quad {\mu J}},{{RR} = \quad {P_{avg}/E_{pp}}}} \\{= \quad {{500\quad {{mW}/300}\quad {\mu J}} = {0.5\quad {W/1} \times 10^{- 4}\quad J}}} \\{= \quad {1,667\quad {pulses}\quad {per}\quad {second}}} \\{= \quad {1.7\quad {kHz}}} \\{{{@500}\quad {\mu J}},{{RR} = \quad {P_{avg}/E_{pp}}}} \\{= \quad {{500\quad {{mW}/500}\quad {\mu J}} = {0.5\quad {W/1} \times 10^{- 4}\quad J}}} \\{= \quad {1,000\quad {pulses}\quad {per}\quad {second}}} \\{= \quad {1.0\quad {kHz}}}\end{matrix}$

[0116] The melanin content of the skin is responsible for thepigmentation of skin. Experimentally it has been demonstrated that thewavelength of least absorption for melanin is in the 800 nm range. Useof this wavelength is important because it is a minimum point ofabsorption for persons of all skin color.

[0117] The above information establishes the parameters required for thelaser 10 used for breast imaging. These parameters are summarized in thetable below. PARAMETERS UNITS Wavelength 700-1100 nm, preferably 800 nmAverage Power 0.5 watt Energy per pulse 100-500 μJ Repetition Rate 1kHz-10 kHz, preferably 1 kHz-5 kHz Pulse Width less than 150 ps,preferably 50-100 ps

[0118] One choice of the laser 10 is a mode-locked titanium:sapphire(Ti:s) laser seeding a Ti:s regenerative amplifier laser.

[0119] Referring to FIG. 23, the laser 10 used in the present inventionis disclosed therein. The laser 10 includes a diode pumped solid-statelaser 204 producing 532 nm light and is used to pump a mode-lockedtitanium:sapphire (Ti:s) laser 206. The output of the laser 206 is inthe 790 to 800 nm wavelength range at a repetition rate of approximately82 Mhz with a pulse width of about 60 picoseconds and is used as a lowpower input to a Ti:s regenerative amplifier 208. The regenerativeamplifier 208 reduces the repetition rate and increases the energy perpulse. The regenerative amplifier 208 is powered by a flash-lamp pumpedlaser 210 producing 532 nm laser pulses at a 1 kHz repetition rate.Various turning mirrors 220 are used to fold the optical path to reducethe space requirement for the lasers.

[0120] The laser 204 is model Millennia, available from Spectra PhysicsCorp., Mountain View, Calif. The laser 206 is Model Tsunami, SpectraPhysics Corp. The laser 208 is model Spitfire, Spectra Physics Corp. Thelaser 210 is model Magellan, Spectra Physics Corp.

[0121] Although laser 10 is disclosed as comprising of severalcomponents, a single laser meeting the required parameters is possible.

[0122] While this invention has been described as having preferreddesign, it is understood that it is capable of further modification,uses and/or adaptations following in general the principle of theinvention and including such departures from the present disclosure ascome within known or customary practice in the art to which theinvention pertains, and as may be applied to the essential features setforth, and fall within the scope of the invention or the limits of theappended claims.

I claim:
 1. CANCELED.
 2. CANCELED.
 3. CANCELED.
 4. CANCELED. 5.CANCELED.
 6. CANCELED.
 7. CANCELED.
 8. CANCELED.
 9. A detector assemblyfor use in a laser imaging apparatus, comprising: a) a housing includinga tubular opening therethrough with an open front end and a rear end;and b) a fiber optic cable having first and second ends, said first endbeing operably associated with said rear end.
 10. A detector assembly asin claim 9, wherein: a) a first lens disposed within said housingintermediate of said front and rear ends; and b) a second lens operablyassociated with said fiber optic cable first end.
 11. A detectorassembly as in claim 10, wherein: a) said first lens is a plano-convexlens.
 12. A detector assembly as in claim 10, wherein: a) said secondlens is a ball lens.
 13. CANCELED.
 14. CANCELED.
 15. CANCELED. 16.CANCELED.
 17. CANCELED.
 18. A laser for imaging human tissue in vivo,comprising: a) said laser has a wavelength of about 800 nm, averagepower of 0.5 w, energy per pulse of about 100-500 μJ, repetition rate ofabout 1 kHz to 5 kHz and pulse width of less than 150 ps.
 19. CANCELED.20. An apparatus for determining the perimeter of an object beingscanned, comprising: a) a scanning chamber for receiving therein anobject being scanned; b) a source of laser beam disposed within saidscanning chamber for impinging on the object being scanned, said laserbeam being adapted to orbit around the object; c) an array of sensorsdisposed within said chamber, each of said sensors being adapted todetect light reflecting from the surface of the object due to said laserbeam exiting from the object; d) each of said sensors being disposedsuch that only one of said sensors generates a peak response to lightemanating from a point on the surface at a predetermined distance from areference point, such that at each angular position of said laser beamin the orbit, a specific point at a distance from the reference isdetermined, thereby to generate a set of points representing theperimeter of the surface after a complete orbit.
 21. An apparatus as inclaim 20, wherein: a) said sensors are CCD sensors.